The disease is named for the presence of sweet-smelling urine, with an odor similar to that of maple syrup. The smell is also present and sometimes stronger in the ear wax of an affected individual. Prior to the easy availability of plasma amino acid measurement, diagnosis was commonly made based on suggestive symptoms and odor. Affected individuals are now often identified with characteristic elevations on plasma amino acids which do not have the characteristic odor.[5] The compound responsible for the odor is sotolon (sometimes spelled sotolone).[6] Infants with this disease seem healthy at birth but if left untreated suffer severe brain damage and eventually die.

Maple syrup urine disease can be classified by its pattern of signs and symptoms, or by its genetic cause. The most common and severe form of the disease is the classic type, which appears soon after birth. Variant forms of the disorder may appear later in infancy or childhood and are typically less severe, but still involve mental and physical problems if left untreated.

Keeping MSUD under control requires careful monitoring of blood chemistry and involves both a special diet and frequent testing.

A diet with minimal levels of the amino acids leucine, isoleucine, and valine must be maintained in order to prevent neurological damage. As these three amino acids are required for proper metabolic function in all humans, specialized protein preparations containing substitutes and adjusted levels of the amino acids have been synthesized and tested, allowing MSUD patients to meet normal nutritional requirements without causing harm.[7] Some patients with MSUD may also improve with administration of high doses of thiamine, a cofactor of the enzyme that causes the condition.

Usually, patients are also monitored by a dietitian. Their diet must be adhered to strictly and permanently. However, with proper management, those afflicted are able to live healthy, normal lives and not suffer the severe neurological damage associated with the disease.

These four genes produce proteins that work together as the branched-chain alpha-keto acid dehydrogenase complex. The complex is essential for breaking down the amino acids leucine, isoleucine, and valine, which are present in many kinds of food (in particular, protein-rich foods such as milk, meat, and eggs). Mutations in any of these genes reduce or eliminate the function of the enzyme complex, preventing the normal breakdown of isoleucine, leucine, and valine. As a result, these amino acids and their by-products build up in the body. Because high levels of these substances are toxic to the brain and other organs, this accumulation leads to the serious medical problems associated with maple syrup urine disease.

This condition has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene - one from each parent - must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder.

On 9 May 2014, the UK National Screening Committee (UK NSC) announced its recommendation to screen every newborn baby in the UK for four further genetic disorders as part of its NHS Newborn Blood Spot Screening programme, including Maple syrup urine disease.[12]